Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 28, 2012; 18(48): 7242-7250
Published online Dec 28, 2012. doi: 10.3748/wjg.v18.i48.7242
Highlights for α-fetoprotein in determining prognosis and treatment monitoring for hepatocellular carcinoma
Xin-Sen Xu, Kai Qu, Chang Liu, Yue-Lang Zhang, Jun Liu, Yan-Zhou Song, Peng Zhang, Si-Nan Liu, Hu-Lin Chang
Xin-Sen Xu, Kai Qu, Chang Liu, Jun Liu, Yan-Zhou Song, Peng Zhang, Si-Nan Liu, Hu-Lin Chang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Yue-Lang Zhang, Department of Radiology, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Author contributions: Xu XS and Qu K contributed equally to this work; Xu XS participated in research design and in the writing of the paper; Qu K participated in the writing of the paper and in literature searches; Liu C participated in research design; Zhang YL participated in research design and revision of the paper, gave much advice about research design, assisted in division of the labor and shared many opinions on the current overview of AFP influence on diagnosis and treatment monitoring in hepatocellular carcinoma; Liu J and Song YZ participated in literature searches; Zhang P, Liu SN and Chang HL participated in data analysis.
Supported by National Natural Science Foundation of China, No. 30872482 and No. 81072051
Correspondence to: Chang Liu, MD, PhD, Professor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China. liuchangdoctor@163.com
Telephone: +86-29-85323900 Fax: +86-29-82654746
Received: July 19, 2012
Revised: August 9, 2012
Accepted: August 26, 2012
Published online: December 28, 2012
Processing time: 195 Days and 23.5 Hours
Abstract

AIM: To explore the prognostic value in the monitoring of treatment efficacy of serial α-fetoprotein (AFP) in hepatocellular carcinoma (HCC) patients.

METHODS: We searched MEDLINE, EMBASE and COCHRANE LIBRARY through April 21, 2012, to find qualifying articles. Our overall search strategy included terms for HCC, AFP, treatment response, and prognosis. Literature was limited to English-language, human studies. Studies reporting cumulative survival rates were summarized qualitatively. For the prognostic meta-analysis, we undertook a series of meta-analyses that summarised the Cox proportional hazard ratios (HRs) by assuming a random effects model. With regards to the correlation of AFP change with radiologic response, the categorical dichotomous variables were assessed using Poisson relative risks (RRs), which were incorporated into the random effects model meta-analysis of accuracy prediction. Between-study heterogeneity was estimated by use of the I² statistic. Publication bias was evaluated using the Begg funnel plot and Egger plot. Sensitivity analyses were conducted first by separating systemic treatment estimates from locoregional therapy estimates, evaluating different AFP response cut-off point effects, and exploring the impact of different study sizes.

RESULTS: Of 142 titles identified in our original search, 11 articles (12 clinical studies) met our criteria. Six studies investigated outcome in a total of 464 cases who underwent systemic treatment, and six studies investigated outcome in a total of 510 patients who received locoregional therapy. A random-effects model meta-analysis showed that AFP response was associated with an mortality HR of 0.55 (95%CI, 0.47-0.65) across HCC in overall survival (OS) and 0.50 (95%CI, 0.38-0.65) in progression-free survival. Restricting analysis to the six eligible analyses of systemic treatment, the pooled HRs were 0.64 (95%CI, 0.53-0.77) for OS. Limiting analysis to the six analyses of locoregional therapy, the pooled HRs for OS was 0.39 (95%CI, 0.29-0.53). We showed a larger pooled HR in the 50% definition studies (HR, 0.67, 95%CI, 0.55-0.83) compared with that from the 20% definition studies (HR, 0.41, 95%CI, 0.32-0.53). Restricting analysis to the four studies including over 100 patients individually, the pooled HR was 0.65 (95%CI, 0.54-0.79), with a pooled HR for OS of 0.35 (95%CI, 0.23-0.46) in the studies of less than 100 patients. As to radiological imaging, 43.1% (155/360) of the patients in the AFP response group presented with a radiological overall response, while the response rate decreased to 11.5% (36/313) in the patients from the AFP nonresponse group. The RR of having no overall response was significantly lower in the AFP response group than the AFP nonresponse group (RR, 0.67; 95%CI, 0.61-0.75). In terms of disease control rate, 86.9% (287/330) in the AFP response group and 51.0% (153/300) in the AFP nonresponse group showed successful disease control, respectively. The RR of disease control failure, similarly, was significantly lower in the AFP response group (RR, 0.37; 95%CI, 0.23-0.58). But these findings could be overestimates because of publication and reporting bias.

CONCLUSION: HCC patients presenting with an AFP response are at decreased risk of mortality. In addition, patients with an AFP response also present with a higher overall response rate and disease control rate.

Keywords: Liver cancer; α-fetoprotein; Response; Prognosis; Monitoring